Platelet-activating factor (PAF) is a chemical mediator of inflammation with an exceedingly high pathologic potential because of its potency and wide spectrum of inflammatory and pharmacologic properties. PAF is synthesized by various inflammatory cells including the human neutrophilic polymorphonuclear leukocyte (PMN) thereby implicating this autacoid in the pathogenesis of acute inflammatory tissue injury. Until recently, human PMN-derived PAF was thought to be only one or two chemically defined molecules (i.e., 1-0-hexadecyl- and/or octadecyl-2-acetyl-sn-glycero-3-phosphocholine, AGEPC). However, recent studies have demonstrated that there is a significant degree of molecular heterogeneity of PMN-derived PAF. These new findings have profound implications regarding the role of this large class of leukocyte-derived phospholipid mediators in the pathogenesis of a variety of cadiovascular and pulmonary disease processes. However, to be able to more clearly define its role in inflammatory tissue injury, the following objectives must first be accomplished: 1) the isolation and identification of the PAF molecules synthesized by human PMN from endogenous phospholipid precursors and from exogenous lyso-phospholipids presented to the PMN as a result of tissue injury; 2) a comprehensive characterization of the biologic activities and potencies of each PAF molecule including platelet, PMN and monocyte stimulation, vasoactive and smooth muscle contracting activities, negative inotropic and arrhythmogenic properties and a variety of cardiovascular and pulmonary alterations; and 3) to determine whether the normally protective acetylhydrolases, which rapidly inactivate AGEPC, are equally as effective in inactivating each PAF molecule. Elucidation of these three objectives will further define the pathologic potential of this class of fascinating acetylated phosphoglyceride mediators.